Epilepsy is a debilitating disorder for millions of Americans, and many are not helped with medications or resective surgery. New therapies are needed. The laboratory of Dr. Steve Potter has recently shown that epileptic activity in neuronal cultures is completely blocked by low-current, low-frequency stimulation from an array of small electrodes. Simultaneously recording neural activity and using it to modify stimulation voltages-that is, using closed-loop feedback to control stimulation-allowed even lower voltages and slower frequencies to block the seizure-like events. The current proposal will extend these findings to live rodents with chronic, spontaneous seizures. Specifically, it is proposed to investigate parameters for effective microstimulation in vivo (using a custom-built stimulator and recording suite), in both normal and epileptic brains, and attempt to suppress epileptiform activity in vivo with both distributed stimulation and closed-loop stimulation. Lastly, since the proposed method relies on recorded action potentials from multiple individual cells, it is proposed to investigate the relation of this single cell activity to the classical seizure measure, the electroencephalogram (EEC), along with local field potentials recorded from high impedance microwires. The methodology uses 32-channel microwire arrays, chronically implanted in the hippocampi or sensorimotor cortex of adult rats, made epileptic with microinjections of tetanus toxin in the same region. The arrays record both cellular action potentials and EEG-like field potentials during the chronic, spontaneous seizures the rodents exhibit. A custom-built stimulator allows simultaneous recording and stimulation from the same implanted set of electrodes. PUBLIC HEALTH RELEVANCE: Many patients with epilepsy continue to experience seizures despite our best medical therapies. Our lab has shown that small arrays of electrodes, recording and stimulating with a state-control algorithm, can completely suppress epileptic activity in cultured brain tissue. This proposal will investigate this treatment in animal models of epilepsy, to validate its safety and efficacy, before beginning clinical trials.